標題: Identification of the common regulators for hepatocellular carcinoma induced by hepatitis B virus X antigen in a mouse model
作者: Lu, Jeng-Wei
Hsia, Yu
Yang, Wan-Yu
Lin, Yu-I
Li, Chao-Chin
Tsai, Ting-Fen
Chang, Ko-Wei
Shieh, Grace S.
Tsai, Shih-Feng
Wang, Horng-Dar
Yuh, Chiou-Hwa
生物科技學系
Department of Biological Science and Technology
公開日期: 1-一月-2012
摘要: Hepatitis B virus X antigen plays an important role in the development of human hepatocellular carcinoma (HCC). The key regulators controlling the temporal downstream gene expression for HCC progression remains unknown. In this study, we took advantage of systems biology approach and analyzed the microarray data of the HBx transgenic mouse as a screening process to identify the differentially expressed genes and applied the software Pathway Studio to identify potential pathways and regulators involved in HCC. Using subnetwork enrichment analysis, we identified five common regulator genes: EDN1, BMP7, BMP4, SPIB and SRC. Upregulation of the common regulators was validated in the other independent HBx transgenic mouse lines. Furthermore, we verified the correlation of their RNA expression levels by using the human HCC samples, and their protein levels by using the human liver disease tissue arrays. EDN1, bone morphogenetic protein (BMP) 4 and BMP7 were upregulated in cirrhosis, BMP4, BMP7 and SRC were further upregulated in hepatocellular or cholangiocellular carcinoma samples. The trend of increasing expression of the common regulators correlates well with the progression of human liver cancer. Overexpression of the common regulators increases the cell viability, promotes migration and invasiveness and enhances the colony formation ability in Hep3B cells. Our approach allows us to identify the critical genes in hepatocarcinogenesis in an HBx-induced mouse model. The validation of the gene expressions in the liver cancer of human patients and their cellular function assays suggests that the identified common regulators may serve as useful molecular targets for the early-stage diagnosis or therapy for HCC.
URI: http://dx.doi.org/10.1093/carcin/bgr224
http://hdl.handle.net/11536/15333
ISSN: 0143-3334
DOI: 10.1093/carcin/bgr224
期刊: CARCINOGENESIS
Volume: 33
Issue: 1
起始頁: 209
結束頁: 219
顯示於類別:期刊論文


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